TEM-based Study of the Phenotype of Astrocytes Differentiated from Induced Pluripotent Stem Cells from a Healthy Donor and a Patient with Parkinson’s Disease

Reprogramming and obtaining of astrocytes from iPSCs received from a donor with a PD-associated mutation in the <i>LRRK2</i> gene allow to assess the nature and dynamics of pathological morphochemical and ultrastructural changes caused by the mutation during gliogenesis. The use of combined techniques (PCR, immunocytochemistry, TEM) to compare cell cultures differentiated from iPSCs allow to assess, on the one hand, general culture parameters, such as the dynamics of culture differentiation based on changes in the expression level of specific genes and immunocytochemical markers, and on the other hand, morphofunctional changes at the level of individual cells. TEM demonstrates significant potential for studying cell cultures differentiated from iPSCs. This technique is instrumental for phenotyping the resulting cells based on their ultrastructure, assessing the degree of their morphological maturity, and identifying minor ultrastructural changes in cells, both pathological and differentiation-associated. The results of this TEM-based study indicate a pronounced decrease in mitochondrial viability and other ultrastructural abnormalities, thus confirming the idea of a significant role of astroglia in the development of the neurodegenerative process in the <i>LRRK2</i>-associated PD; hence, astroglia can be a basis for development of new approaches as well as for searching pharmacological targets in the pathogenetic therapy of the disease.